Genomic Sequencing and Healthcare Dynamics Track Nosocomial SARS-CoV-2 Transmission

Background: Understanding the effectiveness of infection control methods in reducing and preventing SARS-CoV-2 transmission in healthcare settings is of high importance. Infection control is challenging in these environments due to regular contact between healthcare workers (HCWs) and patients. This is amplified by increased frequency of severe adverse responses to SARS-CoV-2 in patients with underlying health conditions.  Methods: We sequenced SARS-CoV-2 genomes for patients and HCWs across multiple geographically distinct UK hospitals. All hospitals were actively enforcing zoning approaches (SARS-CoV-2 negative and SARS-CoV-2 positive areas) as an infection control measure. We integrated patient movement and staff location data into the analysis of viral genome data in order to understand geographical and temporal dynamics of SARS-CoV-2 transmission.  Findings: We obtained 173 high-quality SARS-CoV-2 genomes from patients ( n =134) and HCWs ( n =39). The median number of genomic variants per sample of 11 (range=0-16), with a 61.5% average pairwise similarity in the variants (range=0-100%). Integration of patient movement identified eight patient contact clusters (PCC) with significantly increased similarity in genomic variants compared to non-clustered samples ( p <0.001). Incorporation of HCW location further increased the number of individuals within PCCs. Patients within PCCs carried viruses more genetically identical to HCWs in the same ward location ( p <0.001).  Interpretation: SARS-CoV-2 genome sequencing integrated with patient and HCW movement data increases identification of outbreak clusters and improved understanding of the role of patient-HCW interactions. This dynamic approach to SARS-CoV-2 outbreak monitoring in a healthcare setting is able to support infection control management strategies within the healthcare setting.  Funding:  JME is funded by a postdoctoral research fellowship from Health Education England. WGN is supported by the Manchester NIHR BRC (IS-BRC-1215-20007). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The study was conducted to investigate hospital outbreak investigation/surveillance. Ethical approval was obtained from the Manchester Biomedical Research Centre COVID-19 rapid response group for viral genome analysis.